Ozempic-Class Drug Keeps Appetite Suppressed More Than a Year, Penn Study Finds

Semaglutide, the drug behind Ozempic and Wegovy, continues to suppress appetite and calorie intake more than a year into treatment, according to a new study from the University of Pennsylvania's Center for Weight and Eating Disorders and Penn Metabolic Medicine, published in the American Journal of Clinical Nutrition.

The trial enrolled 120 adults who were overweight or living with obesity, randomly assigning them to receive either a once-weekly 2.4 mg dose of semaglutide or a placebo, both paired with regular lifestyle counseling, over 60 weeks. It is among the first studies to look closely at how the drug affects actual eating behavior well beyond the initial months of treatment, when most prior research has concentrated.

The headline weight-loss numbers were substantial: participants on semaglutide lost an average of 15.1 percent of their starting body weight by week 60, compared with 3.4 percent in the placebo group. But the more novel finding concerned why the weight loss held. Researchers directly measured calorie intake at follow-up visits and found that semaglutide users were consuming 24 to 30 percent fewer calories than the placebo group — a gap that persisted through the full 60 weeks of the study.

That persistence matters because clinicians have observed, anecdotally and in shorter trials, that the drug's most dramatic appetite-blunting effects — patients often describe "food noise" disappearing almost entirely in the first weeks — tend to soften over time. This study found that pattern held true: the early, intense reduction in hunger and food-related intrusive thoughts did become less pronounced as treatment continued. What surprised researchers was that despite that softening, the behavioral effect on actual food intake did not collapse back toward placebo levels. Patients ate less, consistently, even after the initial hunger suppression eased.

The finding adds mechanistic weight to a growing body of research into how GLP-1 receptor agonist drugs work in the brain. Separate research presented this year in mice found that newer oral drugs in the same family reduced pleasure-driven, as opposed to hunger-driven, eating by quieting activity in a deep brain reward circuit — suggesting these drugs may work on two separate fronts: physiological hunger signaling early on, and reward-driven "wanting" of food over the longer term.

For the roughly one in eight American adults who have used a GLP-1 drug for weight loss or diabetes, according to survey estimates, the Penn findings offer reassurance that the drugs' core behavioral effect is not simply a short-lived novelty that fades as the body adapts — a concern that has shadowed the class since early reports of weight regain after patients stop treatment. Researchers cautioned the study was relatively small and did not track outcomes beyond 60 weeks, leaving open questions about calorie intake, weight maintenance and any rebound effects over multi-year use, which is increasingly how the drugs are being prescribed.